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Commentary
Withheld Jeddah & Mecca MERS Sequences Raise
Concerns
Recombinomics Commentary 19:30
May 7, 2014
The above comments from a letter by Christian Drosten posted April 26 on ProMed suggested that Jeddah MERS sequences would be made available almost in real time, as happened during the 2003 SARS-CoV outbreak when sequencing labs posted results on their website.
In 2003 labs in China, Hong Kong, Singapore, Canada, and Taiwan released such sequences almost in real time, and the above comments from the Drosten lab suggested sequences would be quickly posted. This pledge was important because virtually all samples from Jeddah were being sent to his lab, and it was unclear if exported cases from Jeddah to Jordan, Malaysia, Greece, United Arab Emirates, or Egypt would lead to rapid release of the exported sequences.
Shortly after the announcement was made on ProMED, the Drosten lab released three nearly complete sequences from collections in early April at his website (Jeddah_C7569, Jeddah_C7149, Jeddah_C7770), along with a phylogenetic tree that showed that all three Jeddah sequences were virtually identical. Similarly, the Rambaut lab posted a phylogenetic tree which also showed the three sequences were closely related to each other, as well as a camel sequence from Qatar (camel_2). When Recombinomics notified the Rambaut lab that a commentary was being prepared on the results, Andrew Rambaut asked that his tree not be used because the camel_2 sequence had not been made public. He also noted that he was pulling down the tree and asked that Recombinomics post a note that the tree had been made private, which was done.
The initial Recombinomics commentary used the tree posted on the Drosten website, which also showed that the three Jeddah sequences were virtually identical, raising concerns that the sequences from the Jeddah cases represented a novel sub-clade that contained 9 polymorphisms which were in all three human sequences and not reported in any prior human cases.
Another paper was subsequently published with camel sequences from Taif, KSA. Although the accession numbers were given, these sequences could not be accessed at Genbank until this week, but the Rambaut lab was able to put up a new tree with the Taif camel sequences and one of the three human sequences from Jeddah. It is unclear if this representation confused the CDC, because in their telebriefing on the MERS case in Munster, Indiana they noted that there was one sequence from Jeddah cases, when in fact there were three. The CDC cited concerns of an emerging sub-clade, but with only one sequence conclusions couldn’t be drawn.
However, there were three nearly complete sequences, as well as 25 partial spike gene sequences from additional cases in Jeddah, all of which were said to be identical, raising additional concerns that the Jeddah cases were due to the emergence of a novel sub-clade, as happened in 2003 during the SARS CoV outbreak. However, the 25 spike gene sequences were not posted at the Drosten website and the spike positions used in the sequences were not made public. In fact there have been no updates at the Drosten website since the first three sequences were released and the Rambaut website has a phylogenetic tree with only one of the Jeddah sequences.
Recently, an interview of Drosten cited three additional sequences from more recent cases in Jeddah and Mecca, which were said to be “completely normal” which was also used to characterize thre first three Jeddah sequences, raising concerns that the three recent sequences were closely related to the first three sequencing signaling clonal expansion in Jeddah and spread to Mecca.
Attempts to clarify these relationships have failed. A e-mail to the Rambaut lab on May 5 asking about the absence of any new sequences was not answered. Similarly, e-mails to the Drosten and Rambaut labs yesterday and today seeking clarification on the three new sequences also was not answered by either lab.
Publication of the three recent sequences or a phylogenetic tree with the new sequence at the Drosten or Rambaut websites would address the clonal expansion question. The withholding of this information highlights the dangers of allowing one lab to all of the Jeddah sequencing.
These sequences should be released immediately.
The withholding of this information is hazardous to the world’s health.
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